Bioinformatics Glossary

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Secondary structure (protein)

The organization of the peptide backbone of a protein that occurs as a result of hydrogen bonds e.g alpha helix, Beta pleated sheet. 

Selectivity

Selectivity of bioinformatics similarity search algorithms is defined as the significance threshold for reporting database sequence matches. As an example, for BLAST searches, the parameter E is interpreted as the upper bound on the expected frequency of chance occurrence of a match within the context of the entire database search.  E may be thought of as the number of matches one expects to observe by chance alone during the database search. 

Sense strand

The strand of double-stranded DNA that acts as the template strand for RNA synthesis. Typically only one gene product is produced per gene, reading from the sense strand only. (Some viruses have open reading frames in both the sense and the antisense strands). 

Sensitivity

Sensitivity of bioinformatics similarity search algorithms centers around two areas: First, how well can the method detect biologically meaningful relationships between two related sequences in the presence of mutations and sequencing errors; Secondly how does the heuristic nature of the algorithm affect the probability that a matching sequence will not be detected. At the user's discretion, the speed of most similarity search programs can be sacrificed in exchange for greater sensitivity - with an emphasis on detecting lower scoring matches. 

Sequence Tagged Site (STS)

A unique sequence from a known chromosomal location that can be amplified by PCR. STSs act as physical markers for genomic mapping and cloning. 

Sexual PCR (Molecular Diversity)

Sexual PCR is a form of PCR in which similar, but not identical, DNA sequences are reassembled to obtain novel juxtapositions, simulating the result of genetic recombination. The result is the creation of an array of related genes which may possess improved characteristics. By repeated rounds of recombination, selection and PCR-based amplification vastly improved gene-products, such as enzymes with greater activity, may be generated and selected. 

Shotgun cloning

The cloning of an entire gene segment or genome by generating a random set of fragments using restriction endonucleases to create a gene library that can be subsequently mapped and sequenced to reconstruct the entire genome. 

Similarity (homology) search

Given a newly sequenced gene, there are two main approaches to the prediction of structure and function from the amino acid sequence. Homology methods are the most powerful and are based on the detection of significant extended sequence similarity to a protein of known structure, or of a sequence pattern characteristic of a protein family. Statistical methods are less successful but more general and are based on the derivation of structural preference values for single residues, pairs of residues, short oligopeptides or short sequence patterns. The transfer of structure/function information to a potentially homologous protein is straightforward when the sequence similarity is high and extended in length, but the assessment of the structural significance of sequence similarity can be difficult when sequence similarity is weak or restricted to a short region. 

Signal sequence (leader sequence)

A short sequence added to the amino-terminal end of a polypeptide chain that forms an amphipathic helix allowing the nascent polypeptide to migrate through membranes such as the endoplasmic reticulum or the cell membrane. It is cleaved from the polypeptide after the protein has crossed the membrane. 

Single nucleotide polymorphisms (SNPs)

Variations of single base pairs scattered throughout the human genome that serve as measures of the genetic diversity in humans. About 1 million SNPs are estimated to be present in the human genome, and SNPs are useful markers for gene mapping studies. 

Single-pass sequencing

Rapid sequencing of large segments of the genome of an organism by isolating as many expressed (cDNA) sequences as possible and performing single sequencer runs on their 5’ or 3’ ends. Single-pass sequencing typically results in individual, error-prone sequencing reads of 400-700 bases, depending on the type of sequencer used. However, if many of these are generated from numerous clones from different tissues, they may be overlapped and assembled to remove the errors and generate a contiguous sequence for the entire expressed gene. 

Site

Sites in sequences can be located either in DNA (e.g. binding sites, cleavage sites) or in proteins. In order to identify a site in DNA, ambiguity symbols are used to allow several different symbols at one position. Proteins, however, need a different mechanism (see Pattern). Restriction enzyme cleavage sites, for instance, have the following properties:  limited length (typically, less than 20 base pairs); definition of the cleavage site and its appearance (3', 5' overhang or blunt); definition of the binding site. 

Southern blotting

A procedure for the identification of DNA by transmitting a fragment isolated on an agarose gel to a nitrocellulose filter where it can be hybridized with a complementary "probe" sequence. 

Splice form

By using alternative splicing, a single message precursor from DNA can generate an entire family of mRNAs and proteins. This can be utilized to create specificity in cell-cell or cell-ligand interactions. A cell may produce a given protein, but it will be a different splice-form of the protein than that produced by an adjacent cell. In this manner, the two cells have the potential to interact differently with other cells or molecules. Two places where this has been extremely important is in the production of cell-surface specificity proteins in the immune and nervous systems. 

Splice site

The sequence found at the 5’ and 3’ region of exon/intron boundaries, usually defined by a consensus sequence: 

Intron

5’ CAGGTAAGT---------TNCAGG 3’ 

A G C T 

N represents any nucleotide; the bottom line represents alternative nucleotides at the indicated positions. 

Splicing

The joining together of separate DNA or RNA component parts. For example, RNA splicing in eukaryotes involves the removal of introns and the stitching together of the exons from the pre-mRNA transcript before maturation. 

Solvent accessibility

The surface area (typically measured in square angstroms) of a biological molecule, usually a protein, that is exposed to solvent in its native, folded form. Determining the solvent accessibility of a protein helps define which amino acids in its molecular sequence are on the exterior of the molecule, and thus available to participate in interactions with other molecules. 

Structural gene

Gene which encodes a structural protein (cf. Regulatory gene). 

Structure prediction

Algorithms that predict the secondary, tertiary and sometimes even quarternary structure of proteins from their sequences.  Determining protein structure from sequence has been dubbed "the second half of the Genetic Code" since it is the folded tertiary structure of a protein that governs how it functions as a gene product.  As yet most structure prediction methods are only partially successful, and typically work best for certain well-defined classes of proteins. 

Substitution matrix

A model of protein evolution at the sequence level resulting in the development of a set of widely used substitution matrices. These are frequently called Dayhoff, MDM (Mutation Data Matrix), BLOSUM or PAM (Percent Accepted Mutation) matrices. They are derived from global alignments of closely related sequences.  Matrices for greater evolutionary distances are extrapolated from those for lesser ones. 

Subtraction library

A cDNA library that only contains cDNAs uniquely expressed in a given cell or tissue. e.g T cells and B cells will express many common RNAs, as well as a very small percentage which will be unique for T cells and B cells respectively. To make a T cell subtraction library, the cDNA from a T cell library is hybridized with a vast excess of B cell RNA. The commonly expressed genes will result in RNA-cDNA hybrids which can be removed (or subtracted) to leave only T cell specific cDNAs. 

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